The NIH has allocated funds for the establishment of a consortium of academic medical centers to use this collective to discover new underlying mechanisms that link pancreatitis, pancreatic cancer, and diabetes. The University of Florida is perfectly poised to contribute to this consortium. The UFHealth academic medical center has been a regional resource for these diseases for decades, resulting in high clinical volumes. Extensive expertise and translational research infrastructure are already in place. In this application, we demonstrate sustained productivity in the accrual of patients into research studies, high rates of procurement of relevant biospecimens in collaboration with our CTSI biorepository, and independent research efforts into these diseases that anchor our passion to contribute to the consortium. This application also represents an opportunity for increased collaboration between the clinical groups that represent the 3 portals of entry of patients with pancreatitis, diabetes, and pancreatic cancer; the Divisions of Gastroenterology (C. Forsmark, PD/PI), Endocrinology (K. Cusi, PD/PI), and General Surgery (S. Hughes, PD/PI). These investigators, who administratively lead their respective divisions, also represent an alignment of expertise in the diseases of interest (C. Forsmark, pancreatitis; K. Cusi, diabetes, and S. Hughes, pancreatic cancer). Specific Aim 1: To characterize the metabolic profile of patients with coexistent chronic pancreatitis and diabetes mellitus, and establish the role of the underlying metabolic profile, and the effect of treatment, to clinical outcomes. Specific Aim 2: To identify the longitudinal relationship(s) between known genomic variants of genes associated with pancreatitis and disease outcome. Specific Aim 3: To determine how the local inflammatory milieu in chronic pancreatitis and pancreatic cancer is related to disease specific outcomes and the development of diabetes. In summary, this proposed work spans critical areas of knowledge deficit: the role of metabolic profiles/diabetes subtypes to long-term outcomes, metabolomics of Type3c diabetes, genetic mechanisms leading to chronic pancreatitis and possibly pancreatic cancer, and the inflammatory state - both systemic and localized within the pancreas as a potential source of mechanistic contribution to the observed relationships between pancreatitis, pancreatic cancer, and diabetes, diagnostic/prognostic biomarkers and novel therapeutic targets.